Insight into the behavior regulation of drug transfer of nimodipine loaded PLGA microspheres by emulsion evaporation method

Abstract

In the process of preparing microspheres by evaporation of emulsion, drug transfer in the system makes it difficult to control the drug loading and encapsulation efficiency of the product. In this study, Nimodipine loaded microspheres were prepared using poly(lactic-co-glycolic acid) (PLGA) as the matrix materials. The transfer process of drug molecules and solvent molecules in the preparation process were observed by online imaging. Combined with weighing experiments and molecular simulation, three stages of dichloromethane (DCM) diffusion in oil phase were proposed. At 20 °C,15 % and 46 % of DCM content were taken as the critical point, and between the content was slow volatilization stage, which dominated the occurrence of drug reflux and crystallization. The oil phase diffusion and emulsion mass transfer equations of DCM were proposed to judge the influence of each single factor on drug molecular transfer. Low temperature, oil-water ratio and stirring speed could slow down the volatilization of DCM and increase the drug loading and encapsulation efficiency. Low stirring speed could increase the drug loading while avoiding crystallization and reflux, which was the best control factor.